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Direct extrusion of high viscosity pastes containing micron-sized particles at the microscale is a major challenge in the field of additive manufacturing. The nozzle, as a crucial component, has a profound impact on the printing performance through its material composition and structural design. In this study, we have taken into account the influence of Coulomb friction and developed a hydrodynamic model to analyze the flow behavior of high-viscosity pastes within various nozzles. It should be noted that the paste is a composite material with non-Newtonian fluid properties, and its behavior is described by the Herschel–Bulkley constitutive equation. This model provides a clear representation of how the Coulomb friction and structure of the nozzle affect the pressure and velocity distribution during paste extrusion. In addition, experimental studies on the printing performance of various nozzles have shown that the glass nozzle, due to the wall slip phenomenon resulting from its smooth inner surface, can significantly improve the flow velocity and flow rate of the paste. As a result, it enables stable, continuous and high-speed printing. In our experiment, the glass nozzle showed a 100-fold increase in printing speed compared to the dispensing nozzles commonly used in industry, with a printing resolution as fine as 43μm. This result highlights the immense potential of glass nozzles in printing high-viscosity pastes containing micrometer-sized particles.

High extracellular concentrations of adenosine triphosphate (ATP) in the tumor microenvironment generate adenosine by sequential dephosphorylation of CD39 and CD73, resulting in potent immunosuppression to inhibit T cell and natural killer (NK) cell function. CD73, as the determining enzyme for adenosine production, has been shown to correlate with poor clinical tumor prognosis. Conventional inhibitors as analogues of adenosine 5′-monophosphate (AMP) may have a risk of further metabolism to adenosine analogues. Here, we report a new series of malonic acid non-nucleoside inhibitors coordinating with zinc ions of CD73. Compound 12fwas found to be a superior CD73 inhibitor (IC50= 60 nM) by structural optimization, and its pharmacokinetic properties were investigated. In mouse tumor models, compound 12fshowed excellent efficacy and reversal of immunosuppression in combination with chemotherapeutic agents or checkpoint inhibitors, suggesting that it deserves further development as a novel CD73 inhibitor.

ABSTRACT Shear behavior is one aspect of the fundamental mechanical performance of steel fiber reinforced cement-based composites. In order to investigate the influence of fiber orientation on the shear properties [...]

Gut health of broiler chickens is essential for production performance. The present study aimed to evaluate the impact of dietary supplementation with potassium diformate (KDF) on growth performance and intestinal health in broiler chickens. A total of 180 Arbor Acres (AA) broiler chickens were randomly allocated into 3 treatments, with 6 replicates, containing 10 chicks in each replicate. The treatment groups were: control group (CON) was fed a basal diet; KDF-4 groups fed the basal diet with 4 g/kg KDF; KDF-8 groups fed the basal diet with 8 g/kg KDF. The experiment period lasted for 42 d. During the starter phase, the ADFI and F/G of broilers in KDF groups were lower (P< 0.05) compared to the CON group. Furthermore, the BW and ADG in KDF-4 group was improved (P<0.05). The treatment groups exhibited a significant increase (P< 0.05) in both ADG and ADFI during the grower and overall phase. Moreover, the F/G in KDF-4 group was lower (P< 0.05) compared to the CON and KDF-8 groups. The semi-eviscerated weight rate (SEWR), eviscerated carcass weight rate (ECWR), pectoral muscle rate (PMR), and leg muscle rate (LMR) of broilers were improved (P< 0.05) in KDF groups. The serum levels of glucose (GLU) and UREA (UA) were significantly higher (P< 0.05) in KDF-8 group. Additionally, the nutrient apparent utilization rate of dry matter (DM), energy (EE), and crude protein (CP) were improved (P< 0.05) in KDF-4 group. The villus height (VH) and villus height to crypt depth ratio (V/C) of duodenum, jejunum, and ileum were higher (P< 0.05) in KDF groups compared to the CON group, while crypt depth (CD) was significantly reduced (P< 0.05). The digestive enzyme activities of lipase (LIP), amylase (AMS), or trypsin (TPS) were significantly enhanced (P< 0.05) in the intestinal chyme, while the total bacterial count, Escherichia coli, Lactobacilli, Bifidobacteria, and Bacilluswere reduced (P< 0.05) in the ileum. This study demonstrates that the inclusion of KDF in the diet of broilers leads to improvements in growth, slaughter performance, nutrient utilization rate, and maintenance of intestinal health.

AbstractThis study aimed to investigate the effects of dietary supplementation with 5-aminolevulinic acid (5-ALA) on growth performance, blood parameters, iron status, nutrient digestibility, and antioxidant capacity in broilers. A total of 600 one-day-old Arbour Acres broilers were distributed into 5 groups with 6 replicates of 20 birds by a completely randomised design. The birds in the 5 groups were fed the basal diets with 0, 15, 30, 45, and 60 mg/kg 5-ALA, respectively. Dietary supplementation with 60 mg/kg 5-ALA significantly reduced the feed to gain ratio during days 1–21 and days 22–42. Moreover, compared with the control group, dietary supplementation with 30 mg/kg 5-ALA elevated haemoglobin concentrations during days 1–21. Furthermore, dietary supplementation with 45 and 60 mg/kg 5-ALA increased the digestibility of crude protein and decreased serum uric acid levels. At 21 days of age, dietary supplementation with 45 and 60 mg/kg 5-ALA increased liver catalase activity and decreased liver malondialdehyde concentrations, and upregulated the liver mRNA expression of ferritin light chain and nuclear factor erythroid 2-related 2. In addition, the liver mRNA expression of haem oxygenase-1 and divalent metal transporter were upregulated in the 60 mg/kg 5-ALA supplementation group, while the liver mRNA expression of Kelch-like ECH-associated protein 1 was decreased in the 5-ALA supplementation groups. In conclusion, dietary supplementation with 60 mg/kg 5-ALA improved the growth performance, nutrient digestibility, iron status and antioxidant capacity of 21-d-old broilers.HighlightsAddition of 60 mg/kg 5-ALA to broiler diets reduced the feed to gain ratio.Addition of 45 and 60 mg/kg 5-ALA to broiler diets improved crude protein digestibility and decreased serum uric acid levels.5-ALA exhibited antioxidant properties by enhancing the Nrf2 and HO-1 expression

An efficient, large-scale manufacturing process is described for XMT-1864/TFA (1-TFA), an auristatin F derivative, used as a novel, highly potent, cytotoxic warhead in Mersana’s oncology antibody–drug conjugate platforms. The process achieves high diastereomeric purity and controls the impurities with all intermediates readily isolated by crystallization or precipitation in high yield and purity. Protecting groups were selected to ensure tolerability, scalability, and stability of the intermediates under various solution-phase peptide coupling conditions. Crystallization of the final product was developed to remove specified impurities and provide a high-purity active warhead molecule for use in the bioconjugation processing. The convergent synthesis involving six non-GMP steps and five GMP steps has been carried out in multiple cGMP productions on 1-kg scale to produce 1-TFAin >98% chemical purity and <1% total diastereomeric contamination with ∼50% overall yield for the GMP steps.

Trajectory surface hopping combined with ab initio electronic structure calculations is a popular and powerful approach for on-the-fly nonadiabatic dynamics simulations. For large systems, however, this remains a significant challenge because of the unaffordable computational cost of large-scale electronic structure calculations. Here, we present an efficient divide-and-conquer approach to construct the system Hamiltonian based on Wannier analysis and machine learning. In detail, the large system under investigation is first decomposed into small building blocks, and then all possible segments formed by building blocks within a cutoff distance are found out. Ab initio molecular dynamics is carried out to generate a sequence of geometries for each equivalent segment with periodicity. The Hamiltonian matrices in the maximum localized Wannier function (MLWF) basis are obtained for all geometries and utilized to train artificial neural networks (ANNs) for the structure-dependent Hamiltonian elements. Taking advantage of the orthogonality and spatial locality of MLWFs, the one-electron Hamiltonian of a large system at arbitrary geometry can be directly constructed by the trained ANNs. As demonstrations, we study charge transport in a zigzag graphene nanoribbon (GNR), a coved GNR, and a series of hybrid GNRs with a state-of-the-art surface hopping method. The interplay between delocalized and localized states is found to determine the electron dynamics in hybrid GNRs. Our approach has successfully studied GNRs with >10 000 atoms, paving the way for efficient and reliable all-atom nonadiabatic dynamics simulation of general systems.

Herein we develop a new pillar[5]arene-mediated supramolecular polymerization strategy to control the assembly of dyes 4,7-di-2-thienyl-2,1,3-benzothiadiazole and 4,7-di-2-thienyl-2,1,3-benzoselenadiazole in the solid state. The resulting supramolecular polymeric structures drive the dye aggregates in the solid state from parallel alignments to highly ordered “head-to-tail” structures, which effectively suppresses excimer formation and thus aggregation-caused quenching effects and enhances the solid-state emission efficiency by almost 1 order of magnitude. This, together with two-photon excited emission, endows these solid-state polymers with exciting potential in optoelectronic, photonic, and bioimaging applications.

Deoxynivalenol (DON) and zearalenone (ZEN) pose a serious threat to human health, and have been frequently detected in the aqueous environment. To protect consumers from the harm of mycotoxins, a nanozyme-mediated multiplexed lateral flow immunoassay (LFIA) integrated with a smartphone was developed for rapid, highly sensitive and simultaneous quantitative detection of DON and ZEN in the aqueous environment. Highly efficient peroxidase mimicking core-shell Au@Pt nanozymes were synthesized by one-pot method, and then used as signal amplification to highly improve sensitivity of the detection, while a smartphone-based quantitative detection device could rapidly quantify results to improve the detection efficiency of the LIFA for on-site detection. After optimization, the detection time of the assay was 10 min, and the detection limits of the LIFA for DON/ZEN were 0.24/0.04 ng/mL, which were improved 416 and 150 folds compared to the conventional gold nanoparticles (GNPs)-based LFIA. Moreover, there was no obvious cross-reaction with other related mycotoxins, indicating that LFIA had a high specificity. The average recoveries of DON and ZEN from corn, wheat and three water samples were obtained from 94.3 % to 107.9 % with relative standard deviations of 0.2–7.6 %. Furthermore, the accuracy and reliability of the LIFA were evaluated with three spiked water samples, and the results presented good correlations with analytic results from the enzyme-linked immunosorbent assay (R2=0.988 for DON, and 0.983 for ZEN). The results indicate the proposed LIFA was potentially a rapid, on-site simultaneous and highly sensitive method for DON and ZEN detection in the aqueous environment.

The future development of new-type urbanization has drawn great attention from both the government and public alike. In this context, the present study had three related research aims. Firstly, it sought to predict the urbanization and population dynamics in China at both national and provincial levels for the period of 2015 to 2030. Secondly, on this basis, it sought to examine the spatial variation of urbanization given the predicted national urbanization rate of 70.12%. Thirdly, it sought to estimate and evaluate the national and provincial demands of investment in the development of new-type urbanization. The main conclusions from this study were as follows: (1) The population size and urbanization rate will reach 1.445 billion and 70.12%, respectively, from 2015 to 2030. (2) The demographic dividend will vanish when the population pressure reaches its maximum. During this period, there will be 70.16 million urban population born. The suburban population that becomes urbanized will be 316.7 million, and thus the net increase in urban population will reach 386 million. (3) Although the urbanization rate of every Chinese province will increase during 2015–2030, it will do so unequally, while differences in urbanization quality among provinces will also be substantial. In some provinces, moreover, the urbanization quality is not compatible with their eco-social development. (4) A total of 4,105,380 billion yuan is required to fund new-type urbanization and the investment demand for each province varies greatly; for example, Guangdong province requires the most funding, amounting to approximately 148 times that required by Tibet, the province in least need of funding. In the final part of this study, policy suggestions concerning the investment of the new-type urbanization are put forward and discussed.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis. The aim of this study was to investigate SFTS virus (SFTSV) infections in ticks in Northeastern China. A total of 6427 ticks, including 5450 Haemaphysalis longicornis, 463 Dermacentor silvarum, 351 Dermacentor nuttalli, and 163 Ixodes persulcatus, were sampled in the Liaoning, Jilin, and Heilongjiang Provinces of Northeastern China. Viral megagenomic analysis of the ticks revealed 25 contigs targeting the M and L segments of the SFTSV genome. H. longicorniscollected from Jinxing, Jilin Province, were analyzed by RT-PCR, which showed positive results for SFTSV, with a minimum prevalence of 3.0%. The full-length sequence of the S, M, and L segments of the SFTSV were obtained, and phylogenetic analysis showed that the virus strain found in Jilin formed a monophyletic cluster with the SFTSV strains from Jiangsu, suggesting that SFTSV in the Jilin Province may have spread from the Jiangsu Province. These findings are the first to demonstrate molecular evidence of SFTSV in ticks in the Jilin Province of Northeastern China and indicate the need for measures to prevent and control SFTS.

Toxoplasma gondiican infect almost all warm-blooded animals, and many serological methods have been developed to detect T. gondiiinfection in a variety of animal species. In the present study, the seroprevalence of T. gondiiinfection in farmed mink in northeast China was determined using the modified agglutination test (MAT), a Western blot (WB), and 3 enzyme-linked immunosorbent assays (ELISAs) with protein A/G conjugate, using either of 2 recombinant dense granule antigens, GRA1 and GRA7, or Toxoplasmasoluble antigens (TSA). There was no significant difference between the detection results of the GRA1-, GRA7-, and TSA-ELISAs and WB (McNemar chi-square, P> 0.05), but a significant difference was observed between MAT and WB (P< 0.05). A near perfect agreement (97.0%) was found between the GRA7-ELISA and WB (κ = 0.83), and a substantial agreement (92.4–93.1%) was observed in the TSA- and GRA1-ELISAs (κ = 0.68–0.73). The GRA7-ELISA showed the highest sensitivity and specificity, and the lowest false-positive and negative rates, while the MAT gave both a low sensitivity and frequent false positives in comparison to the WB. Receiver operating characteristic analysis revealed the largest area under curve of 0.85 (95% confidence interval: 0.74–0.96), and the highest relative sensitivity (72.7%) and specificity (99.0%) for a cutoff value of 0.19 in the GRA7-ELISA. These results indicate that the GRA7-ELISA is suitable for detection of T. gondiiinfection in mink and that MAT should be used with caution.

AbstractThe precise detection of Toxoplasma gondiiinfection in cattle has important public health significance. In the present study, recombinant granule antigen protein GRA7 was evaluated as a potential diagnostic marker for T. gondiiinfection in cattle by an indirect enzyme-linked immunosorbent assay (ELISA) using the reference serum samples determined by immunofluorescence assay and Western blotting, showing that GRA7-ELISA has a sensitivity of 96.4%, and a specificity of 98.6%. The detection results by GRA7- and Toxoplasmalysate antigen–based ELISAs were compared, indicating that no significant difference (p>0.05) and perfect agreement (κ=0.74) was observed between the two tests. Receiver operating characteristic analysis showed a relative sensitivity and specificity of 100% and 97.3% at the cut-off value of 0.3 for GRA7-ELISA. These data demonstrate that GRA7 is a promising serodiagnostic marker for T. gondiiinfection in cattle.

A series of study on self-sustained electrochemical promotion (SSEP) catalysts are summarized. The SSEP catalyst enables more than 90% conversion and 90% hydrogen sensitivity at temperatures of 450 - 650 oC for methane and n-pentadecane reforming. The conversion and sensitivity is up to two orders of magnitude greater than those over Ni based catalyst and a commercial Pt catalyst at 450-550degC. The kinetic models incorporating Langmuir-Hinshelwood model and SSEP effect successfully describe the major characteristics of hydrocarbons reforming over the SSEP catalyst. This concept of SSEP catalyst may provide a new route for developing high performance catalysts for hydrocarbons reforming.

We report the first aqueous process fabrication of thick, flexible, and fully compressed lithium ion battery cathodes exceeding 200 um in thickness using an adhesive, elastomeric, and ionically conductive PEG-based copolymer binder. The binder was synthesized through the statistical copolymerization of poly(ethylene glycol) methyl ether methacrylates (PEGMA), methyl methacrylate (MMA), and isobutyl vinyl ether (IBVE) in optimal proportions. Using standard LiCoO2 as active material, dense and flexible cathode films can withhold active mass loadings over 30 mg/cm2 which deliver 4.53 mAh/cm2 with 94% capacity retention at C/2-rate. Electrodes were fabricated by casting aqueous cathode slurries onto nickel foam, followed by drying and hard calendar compression at 10 tons/cm2. Coordinating the binder with lithium salt plays a crucial role in activating the cathode.

In-field surface contamination and moisture detection is one of the critical issues in preparation of adhesive bonds between composite adherends for aircraft manufacture. In this paper, the feasibility of an all solid-sate electrochemical sensor technology is explored. Redox pairs or mediators are combined into a solid-state electrolyte, NafionTM. The output current in response to a cyclic polarization is used as the indication of the surface contamination level. Electrochemical impedance spectroscopy measurements using the sensors made were conducted. The results indicate that the small amount of moisture and/or sulfuric acid on initially cleaned and vacuumed polymer surfaces results in about 10 times increment of the peak current in cyclic voltammetry tests.

Feed intake is a major factor in maintaining the balance between ruminal fermentation and the microbial community of dairy cows. To explore the relationship among feed intake, microbial metabolism, and ruminal fermentation, we examined the combined signatures of the microbiome and metabolome in dairy cows with different feed intake levels. Eighteen dairy cows were allocated to high feed intake (HFI), medium feed intake (MFI), and low feed intake (LFI) groups according to their average daily feed intake. 16S rDNA sequencing results revealed that the relative abundance of Firmicutes in the HFI group was significantly higher than that in the MFI and LFI groups (P < 0.05). The ratio of Bacteroidetes to Firmicutes was significantly lower in the HFI group than in the MFI and LFI groups (P < 0.05). The relative abundance of Lachnospiraceae_unclassified, Veillonellaceae_unclassified, and Saccharofermentants was significantly higher in the HFI group than in the LFI and MFI groups (P < 0.05). The relative abundance of Erysipelotrichaceae_unclassified and Butyrivibrio was significantly higher in the HFI group than in the MFI and LFI groups (P < 0.05). Ultra high performance liquid chromatography-mass spectrometry revealed five key pathways, including the linoleic acid metabolism pathway, alpha-linolenic acid metabolism, arginine and proline metabolism, glutathione metabolism, and valine, leucine, and isoleucine biosynthesis, which are closely related to energy and amino acid metabolism. Linoleic acid, glutamate, alpha-linolenic acid, l-methionine, and l-valine levels were significantly lower in the HFI group than in the MFI and LFI groups (q < 0.05), while the relative content of glutamate was significantly lower in the MFI group than in the LFI group (q < 0.05). Stearic acid content was significantly higher in the HFI group than in the LFI group (q < 0.05). Our findings provide insight into the rumen microbiome of dairy cows with different feed intake and the metabolic pathways closely associated with feed intake in early-lactating cows. The candidates involved in these metabolic pathways may be useful for identifying variations in feed intake. The signatures of the rumen microbiome and metabolome in dairy cows may help make decisions regarding feeding.